Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9VGDIP)

• DOT Name: Interleukin-19 (IL19)
• Synonyms: IL-19; Melanoma differentiation-associated protein-like protein; NG.1
• Gene Name: IL19
• UniProt ID: IL19_HUMAN
• PDB ID: 1N1F
• Pfam ID: PF00726
• Sequence:
  MKLQCVSLWLLGTILILCSVDNHGLRRCLISTDMHHIEESFQEIKRAIQAKDTFPNVTIL
  STLETLQIIKPLDVCCVTKNLLAFYVDRVFKDHQEPNPKILRKISSIANSFLYMQKTLRQ
  CQEQRQCHCRQEATNATRVIHDNYDQLEVHAAAIKSLGELDVFLAWINKNHEVMFSA
• Function: Cytokine that functions as an anti-inflammatory and proangiogenic factor. Polarizes adaptive immunity to an anti-inflammatory phenotype through induction of T-helper 2 responses by both down-regulation of IFN-gamma and up-regulation of IL4 and IL13. Produced by osteocytes, stimulates granulopoiesis and neutrophil formation. Exerts its biological effect through a receptor complex consisting of a heterodimer of IL20RA and IL20RB. In turn, activates the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway, and importantly, STAT3.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-20 family signaling (R-HSA-8854691)

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the secretion of Interleukin-19 (IL19).	[1]
Cidofovir	DMA13GD	Approved	Cidofovir increases the secretion of Interleukin-19 (IL19).	[1]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the secretion of Interleukin-19 (IL19).	[1]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the secretion of Interleukin-19 (IL19).	[1]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interleukin-19 (IL19).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Interleukin-19 (IL19).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Interleukin-19 (IL19).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Interleukin-19 (IL19).	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interleukin-19 (IL19).	[4]

References

• [1] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [2] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [3] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [5] Development of human retinal organoid models for bisphenol toxicity assessment. Ecotoxicol Environ Saf. 2022 Oct 15;245:114094. doi: 10.1016/j.ecoenv.2022.114094. Epub 2022 Sep 18.